Search

The occurrence of severe adverse events such as progressive multifocal leukoencephalopathy (PML) has the potential to limit the benefits of highly efficacious medicines being developed to fulfill unmet clinical needs across therapeutic areas. Following an Expert meeting in London in July 2011 (http://www.ema.europa.eu/docs/en_GB/document_library/Report/2011/09/WC500111562.pdf), a research agenda, highlighting methodological, clinical, and communication elements, to mitigate the risk and improve the management of drug-induced PML has been agreed upon. [ABSTRACT FROM AUTHOR]

The study of above- and below-ground organ plant coordination is crucial for understanding the biophysical constraints and trade-offs involved in species’ performance under different environmental conditions. Environmental stress is expected to increase constraints on species trait combinations, resulting in stronger coordination among the organs involved in the acquisition and processing of the most limiting resource. To test this hypothesis, we compared the coordination of trait combinations in 94 tree seedling species from two tropical forest systems in Mexico: dry and moist. In general, we expected that the water limitation experienced by dry forest species would result in stronger leaf-stem-root coordination than light limitation experienced by moist forest species. Using multiple correlations analyses and tools derived from network theory, we found similar functional trait coordination between forests. However, the most important traits differed between the forest types. While in the dry forest the most central traits were all related to water storage (leaf and stem water content and root thickness), in the moist forest they were related to the capacity to store water in leaves (leaf water content), root efficiency to capture resources (specific root length), and stem toughness (wood density). Our findings indicate that there is a shift in the relative importance of mechanisms to face the most limiting resource in contrasting tropical forests.

Abstract The international CIHLMU Occupational Safety and Health Symposium 2019 was held on 16th March, 2019 at the Ludwig-Maximilians-Universität Munich, Germany. About 60 participants from around the world representing occupational health and safety professionals, students, instructors from several institutions in Germany and abroad, attended the symposium. The main objective of the symposium was to create awareness on global challenges and opportunities in work-related respiratory diseases. One keynote lecture and six presentations were made. While the keynote lecture addressed issues on occupational diseases in the twenty-first century, the six presentations were centered on: Prevention and control of work-related respiratory diseases, considerations; Occupational health and safety in Mining: Respiratory diseases; The prevention of TB among health workers is our collective responsibility; Compensation and prevention of occupational diseases and discussion on how artificial intelligence can support them: Overview of international approaches; Work-related Asthma: Evidence from high-income countries; and The role of imaging in the diagnosis of work- related respiratory diseases. A panel discussion was conducted following the presentations on the importance and challenges of data acquisition which is needed to have a realistic picture of the occupational safety and health status of workers at different levels. The current summary is an attempt to share the proceedings of the symposium.

Systemic therapies for pancreatic ductal adenocarcinoma (PDAC) remain unsatisfactory. Clinical prognosis is particularly poor for tumor subtypes with activating aberrations in the MYC pathway, creating an urgent need for novel therapeutic targets. To unbiasedly find MYC-associated epigenetic dependencies, we conducted a drug screen in pancreatic cancer cell lines. Here, we found that protein arginine N-methyltransferase 5 (PRMT5) inhibitors triggered an MYC-associated dependency. In human and murine PDACs, a robust connection of MYC and PRMT5 was detected. By the use of gain- and loss-of-function models, we confirmed the increased efficacy of PRMT5 inhibitors in MYC-deregulated PDACs. Although inhibition of PRMT5 was inducing DNA damage and arresting PDAC cells in the G2/M phase of the cell cycle, apoptotic cell death was executed predominantly in cells with high MYC expression. Experiments in primary patient-derived PDAC models demonstrated the existence of a highly PRMT5 inhibitor–sensitive subtype. Our work suggests developing PRMT5 inhibitor–based therapies for PDAC.

Product information (PI) is a vital part of any medicinal product approved for use within the European Union and consists of a summary of products characteristics (SmPC) for healthcare professionals and package leaflet (PL) for patients, together with the product packaging. In this study, based on the English corpus of the EMA product information documents for all centrally approved medicinal products within the EU, a BERT sentence embedding model was used together with clustering and dimensional reduction techniques to identify sentence similarity clusters that could be candidates for standardization. A total of 1258 medicinal products were included in the study. From these, a total of 783 K sentences were extracted from SmPC and PL documents which were aggregated into a total of 284 and 129 semantic similarity clusters, respectively. The spread distribution among clusters shows separation into different cluster types. Examples of clusters with low spread include those with identical word embeddings due to current standardization, such as section headings and standard phrases. Others show minor linguistic variations, while the group with the largest variability contains variable wording but with significant semantic overlap. The sentence clusters identified could serve as candidates for further standardization of the PI. Moving from free text human wording to auto-generated text elements based on multiple-choice input for appropriate parts of the package leaflet and summary of product characteristics, could reduce both time and complexity for applicants as well as regulators, and ultimately provide patients and prescribers with documents that are easier to understand and better adapted for search availabilities.

OBJECTIVE:To analyze the pattern and appropriateness of pain medications in older adults receiving home care. METHODS:We performed a prospective cross-sectional study in patients ≥65 years old having chronic pain and receiving home care in Berlin, Germany. Data on prescribed pain medications were collected using self-reported information, nursing documents, and medication plans during interviews at home. Pain intensity was determined with the numeric rating scale (NRS) and the Pain Assessment In Advanced dementia (PAINAD) scale. The Pain Medication Appropriateness Scale score (SPMAS) was applied to evaluate inappropriateness (i.e. a score ≤67) of pain medication. RESULTS:Overall 322 patients with a mean age of 82.1 ± 7.4 years (71.4% females) were evaluated. The average pain intensity scores during the last 24 hours were 5.3 ± 2.1 and 2.3 ± 2.3 on NRS and PAINAD scale (range 0-10, respectively). Sixty (18.6%) patients did not receive any pain medication. Among the treated patients, dipyrone was the most frequently prescribed analgesic (71.4%), while 50.8% and 19.1% received systemic treatment with opioids and non-steroidal anti-inflammatory drugs, respectively. The observed median SPMAS was 47.6 (range 0-100) with 58 (18.0%) of patients achieving appropriate values. Half of the patients were treated with scheduled, while 29.9% were only treated with on-demand medications. Cognitive status had no effect on appropriateness of pain treatment. CONCLUSIONS:We observed substantial deficits in dosing patterns and appropriateness of pain medication in older adults with pain receiving home care. This applied to both patients with and without severe cognitive impairment.

Background: Rapid Point-Of-Care Tests for Chlamydia trachomatis (CT) may reduce onward transmission and reproductive sexual health (RSH) sequelae by reducing turnaround times between diagnosis and treatment. The io® single module system (Atlas Genetics Ltd.) runs clinical samples through a nucleic acid amplification test (NAAT)-based CT cartridge, delivering results in 30 min. Methods: Prospective diagnostic accuracy study of the io® CT-assay in four UK Genito-Urinary Medicine (GUM)/RSH clinics on additional-to-routine self-collected vulvovaginal swabs. Samples were tested “fresh” within 10 days of collection, or “frozen” at −80 °C for later testing. Participant characteristics were collected to assess risk factors associated with CT infection. Results: CT prevalence was 7.2% (51/709) overall. Sensitivity, specificity, positive and negative predictive values of the io® CT assay were, respectively, 96.1% (95% Confidence Interval (CI): 86.5–99.5), 97.7% (95%CI: 96.3–98.7), 76.6% (95%CI: 64.3–86.2) and 99.7% (95%CI: 98.9–100). The only risk factor associated with CT infection was being a sexual contact of an individual with CT. Conclusions: The io® CT-assay is a 30-min, fully automated, high-performing NAAT currently CE-marked for CT diagnosis in women, making it a highly promising diagnostic to enable specific treatment, initiation of partner notification and appropriately intensive health promotion at the point of care.